The impact of activated p-AKT expression on clinical outcomes in diffuse large B-cell lymphoma: A clinicopathological study of 262 cases

J. Y. Hong; M. E. Hong; M. K. Choi; Y. S. Kim; W. Chang; C. H. Maeng; S. Park; S. J. Lee; I. G. Do; J. S. Jo; S. H. Jung; S. J. Kim; Y. H. Ko; W. S. Kim

doi:10.1093/annonc/mdt530

The impact of activated p-AKT expression on clinical outcomes in diffuse large B-cell lymphoma: A clinicopathological study of 262 cases

J. Y. Hong, M. E. Hong, M. K. Choi, Y. S. Kim, W. Chang, C. H. Maeng, S. Park, S. J. Lee, I. G. Do, J. S. Jo, S. H. Jung, S. J. Kim, Y. H. Ko, W. S. Kim

Department of Internal Medicine

Research output: Contribution to journal › Article › peer-review

31 Scopus citations

Abstract

Background: Oncogenic phosphatidylinositol-3-kinase/serine-threonine kinase (PI3K/AKT) pathway plays a critical role in cell proliferation and growth. Phosphorylated AKT (p-AKT) has been reported to be abnormally overexpressed and to have poor prognostic impact in solid tumors. Patients and methods: To define the clinical implications of p-AKT expression in diffuse large B-cell lymphoma (DLBCL), we calculated arbitrary units (AUs) by multiplying the intensity and the proportion of p-AKT expression and investigated the impact of p-AKT expression on clinical outcomes. We assessed 262 patients with DLBCL. Based on a cutoff value of the upper limit of the third quartile of AUs, 56 patients were classified as high p-AKT and the remaining 206 patients were classified as low p-AKT. Results: The high p-AKT group was closely associated with more advanced stage (stage III-IV, P = 0.02), two or more extranodal involvement (P = 0.03), lactic dehydrogenase elevation (P = 0.03), higher International Prognostic Index risk groups (high intermediate/high, P = 0.02), and the presence of B-symptoms (P = 0.01). The high p-AKT group showed substantially worse overall survival (OS) (median OS, 115.0 months versus not reached, P = 0.004) and progression-free survival (PFS) (median PFS, 25.5 versus 105.8 months, P = 0.019) compared with the low p-AKT group. Multivariate analysis revealed that high p-AKT expression retained its significant poor prognostic impact for OS (hazard ratio 1.7; 95% confidence interval, 1.0-2.7; P = 0.031). The subgroup with high p-AKT expression and concurrent Epstein-Barr virus positivity showed worst prognosis with the median OS and PFS of 15.2 and 7.4 months. Conclusion: DLBCL patients with high p-AKT expression showed distinct clinical features and followed a more rapidly deteriorating clinical course with worse OS and PFS. Thus, a more effective treatment option should be developed for this subset of DLBCL patients, and targeting PI3K/AKT pathway may be a promising therapeutic strategy.

Original language	English
Pages (from-to)	182-188
Number of pages	7
Journal	Annals of Oncology
Volume	25
Issue number	1
DOIs	https://doi.org/10.1093/annonc/mdt530
State	Published - Jan 2014

Keywords

Diffuse large b-cell lymphoma
P-AKT
PI3K/AKT pathway

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10.1093/annonc/mdt530

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Hong, J. Y., Hong, M. E., Choi, M. K., Kim, Y. S., Chang, W., Maeng, C. H., Park, S., Lee, S. J., Do, I. G., Jo, J. S., Jung, S. H., Kim, S. J., Ko, Y. H., & Kim, W. S. (2014). The impact of activated p-AKT expression on clinical outcomes in diffuse large B-cell lymphoma: A clinicopathological study of 262 cases. Annals of Oncology, 25(1), 182-188. https://doi.org/10.1093/annonc/mdt530

@article{375c29bfd15d4b4cad65b9df8a01a6e2,

title = "The impact of activated p-AKT expression on clinical outcomes in diffuse large B-cell lymphoma: A clinicopathological study of 262 cases",

abstract = "Background: Oncogenic phosphatidylinositol-3-kinase/serine-threonine kinase (PI3K/AKT) pathway plays a critical role in cell proliferation and growth. Phosphorylated AKT (p-AKT) has been reported to be abnormally overexpressed and to have poor prognostic impact in solid tumors. Patients and methods: To define the clinical implications of p-AKT expression in diffuse large B-cell lymphoma (DLBCL), we calculated arbitrary units (AUs) by multiplying the intensity and the proportion of p-AKT expression and investigated the impact of p-AKT expression on clinical outcomes. We assessed 262 patients with DLBCL. Based on a cutoff value of the upper limit of the third quartile of AUs, 56 patients were classified as high p-AKT and the remaining 206 patients were classified as low p-AKT. Results: The high p-AKT group was closely associated with more advanced stage (stage III-IV, P = 0.02), two or more extranodal involvement (P = 0.03), lactic dehydrogenase elevation (P = 0.03), higher International Prognostic Index risk groups (high intermediate/high, P = 0.02), and the presence of B-symptoms (P = 0.01). The high p-AKT group showed substantially worse overall survival (OS) (median OS, 115.0 months versus not reached, P = 0.004) and progression-free survival (PFS) (median PFS, 25.5 versus 105.8 months, P = 0.019) compared with the low p-AKT group. Multivariate analysis revealed that high p-AKT expression retained its significant poor prognostic impact for OS (hazard ratio 1.7; 95% confidence interval, 1.0-2.7; P = 0.031). The subgroup with high p-AKT expression and concurrent Epstein-Barr virus positivity showed worst prognosis with the median OS and PFS of 15.2 and 7.4 months. Conclusion: DLBCL patients with high p-AKT expression showed distinct clinical features and followed a more rapidly deteriorating clinical course with worse OS and PFS. Thus, a more effective treatment option should be developed for this subset of DLBCL patients, and targeting PI3K/AKT pathway may be a promising therapeutic strategy.",

keywords = "Diffuse large b-cell lymphoma, P-AKT, PI3K/AKT pathway",

author = "Hong, {J. Y.} and Hong, {M. E.} and Choi, {M. K.} and Kim, {Y. S.} and W. Chang and Maeng, {C. H.} and S. Park and Lee, {S. J.} and Do, {I. G.} and Jo, {J. S.} and Jung, {S. H.} and Kim, {S. J.} and Ko, {Y. H.} and Kim, {W. S.}",

year = "2014",

month = jan,

doi = "10.1093/annonc/mdt530",

language = "English",

volume = "25",

pages = "182--188",

journal = "Annals of Oncology",

issn = "0923-7534",

publisher = "Elsevier Ltd.",

number = "1",

}

TY - JOUR

T1 - The impact of activated p-AKT expression on clinical outcomes in diffuse large B-cell lymphoma

T2 - A clinicopathological study of 262 cases

AU - Hong, J. Y.

AU - Hong, M. E.

AU - Choi, M. K.

AU - Kim, Y. S.

AU - Chang, W.

AU - Maeng, C. H.

AU - Park, S.

AU - Lee, S. J.

AU - Do, I. G.

AU - Jo, J. S.

AU - Jung, S. H.

AU - Kim, S. J.

AU - Ko, Y. H.

AU - Kim, W. S.

PY - 2014/1

Y1 - 2014/1

N2 - Background: Oncogenic phosphatidylinositol-3-kinase/serine-threonine kinase (PI3K/AKT) pathway plays a critical role in cell proliferation and growth. Phosphorylated AKT (p-AKT) has been reported to be abnormally overexpressed and to have poor prognostic impact in solid tumors. Patients and methods: To define the clinical implications of p-AKT expression in diffuse large B-cell lymphoma (DLBCL), we calculated arbitrary units (AUs) by multiplying the intensity and the proportion of p-AKT expression and investigated the impact of p-AKT expression on clinical outcomes. We assessed 262 patients with DLBCL. Based on a cutoff value of the upper limit of the third quartile of AUs, 56 patients were classified as high p-AKT and the remaining 206 patients were classified as low p-AKT. Results: The high p-AKT group was closely associated with more advanced stage (stage III-IV, P = 0.02), two or more extranodal involvement (P = 0.03), lactic dehydrogenase elevation (P = 0.03), higher International Prognostic Index risk groups (high intermediate/high, P = 0.02), and the presence of B-symptoms (P = 0.01). The high p-AKT group showed substantially worse overall survival (OS) (median OS, 115.0 months versus not reached, P = 0.004) and progression-free survival (PFS) (median PFS, 25.5 versus 105.8 months, P = 0.019) compared with the low p-AKT group. Multivariate analysis revealed that high p-AKT expression retained its significant poor prognostic impact for OS (hazard ratio 1.7; 95% confidence interval, 1.0-2.7; P = 0.031). The subgroup with high p-AKT expression and concurrent Epstein-Barr virus positivity showed worst prognosis with the median OS and PFS of 15.2 and 7.4 months. Conclusion: DLBCL patients with high p-AKT expression showed distinct clinical features and followed a more rapidly deteriorating clinical course with worse OS and PFS. Thus, a more effective treatment option should be developed for this subset of DLBCL patients, and targeting PI3K/AKT pathway may be a promising therapeutic strategy.

AB - Background: Oncogenic phosphatidylinositol-3-kinase/serine-threonine kinase (PI3K/AKT) pathway plays a critical role in cell proliferation and growth. Phosphorylated AKT (p-AKT) has been reported to be abnormally overexpressed and to have poor prognostic impact in solid tumors. Patients and methods: To define the clinical implications of p-AKT expression in diffuse large B-cell lymphoma (DLBCL), we calculated arbitrary units (AUs) by multiplying the intensity and the proportion of p-AKT expression and investigated the impact of p-AKT expression on clinical outcomes. We assessed 262 patients with DLBCL. Based on a cutoff value of the upper limit of the third quartile of AUs, 56 patients were classified as high p-AKT and the remaining 206 patients were classified as low p-AKT. Results: The high p-AKT group was closely associated with more advanced stage (stage III-IV, P = 0.02), two or more extranodal involvement (P = 0.03), lactic dehydrogenase elevation (P = 0.03), higher International Prognostic Index risk groups (high intermediate/high, P = 0.02), and the presence of B-symptoms (P = 0.01). The high p-AKT group showed substantially worse overall survival (OS) (median OS, 115.0 months versus not reached, P = 0.004) and progression-free survival (PFS) (median PFS, 25.5 versus 105.8 months, P = 0.019) compared with the low p-AKT group. Multivariate analysis revealed that high p-AKT expression retained its significant poor prognostic impact for OS (hazard ratio 1.7; 95% confidence interval, 1.0-2.7; P = 0.031). The subgroup with high p-AKT expression and concurrent Epstein-Barr virus positivity showed worst prognosis with the median OS and PFS of 15.2 and 7.4 months. Conclusion: DLBCL patients with high p-AKT expression showed distinct clinical features and followed a more rapidly deteriorating clinical course with worse OS and PFS. Thus, a more effective treatment option should be developed for this subset of DLBCL patients, and targeting PI3K/AKT pathway may be a promising therapeutic strategy.

KW - Diffuse large b-cell lymphoma

KW - P-AKT

KW - PI3K/AKT pathway

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U2 - 10.1093/annonc/mdt530

DO - 10.1093/annonc/mdt530

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AN - SCOPUS:84905406380

SN - 0923-7534

VL - 25

SP - 182

EP - 188

JO - Annals of Oncology

JF - Annals of Oncology

IS - 1

ER -

The impact of activated p-AKT expression on clinical outcomes in diffuse large B-cell lymphoma: A clinicopathological study of 262 cases

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Keywords

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